Legionella pneumophila is a significant human lung pathogen that is responsible for many community- and hospital- acquired cases of pneumonia. An important part of the pathogenesis of Legionella infection is its ability to grow inside of macrophages. Interestingly, different inbred strains of mice exhibit differences in the permissiveness of their macrophages for the intracellular replication of Legionella, and these differences have been attributed to genetic differences in one of the mouse Neuronal Apoptosis Inhibitory Protein (Naip) genes. The goals of this project are to: Establish the identity of the Naip gene and its mutations that are responsible for the differences in Legionella permissiveness, and to study the function of the Naip proteins by identifying critical interacting proteins that participate in its molecular function.